Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients.

Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285 292 patients were included in the 6 matched cohorts: 57 929 apixaban-warfarin, 26 838 dabigatran-warfarin, 83 007 rivaroxaban-warfarin, 27 096 apixaban-dabigatran, 62 619 apixaban-rivaroxaban, and 27 538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.

Evaluating the Effect of Treatment Persistence on the Economic Burden of Moderate to Severe Psoriasis and/or Psoriatic Arthritis Patients in the U.S. Department of Defense Population.

BACKGROUND: Psoriasis is a chronic, hyper-proliferative dermatological condition associated with joint symptoms known as psoriatic arthritis (PsA). In a 2013 review, the total economic burden of PsA was estimated at $51.7-$63.2 billion. The economic burden of moderate to severe psoriasis patients has reduced significantly with the advent of biologics, but there remains a dearth of real-world evidence of the impact of treatment persistence on the economic burden of moderate to severe psoriasis and/or PsA patients. OBJECTIVE: To evaluate the overall and psoriasis and/or PsA-related health care utilization and costs among patients who were persistent versus those nonpersistent on index biologic among the moderate to severe psoriasis and/or PsA population. METHODS: Adult patients with ≥ 2 claims with diagnosis of psoriasis and/or PsA during the period of November 2010-October 2015 were identified from the U.S. Department of Defense database; the first diagnosis date during November 2011-October 2014 was defined as the index date. As of the index date, patients were considered to have moderate to severe psoriasis or PsA if they had ≥ 1 nontopical systemic therapy or phototherapy during the 1-year pre- or 1-month post-index date. Persistence to index therapy, defined as the first biologic used (etanercept, adalimumab, ustekinumab, infliximab) on or within 30 days post-index date, was determined based on the biologic dosing schedule and a 90-day gap. Generalized linear models were used to compare the health care utilization and costs between persistent and nonpersistent patients during the 1-year post-index period. RESULTS: A total of 2,945 moderate to severe psoriasis and/or PsA patients were identified. Of those, 1,899 (64.5%) were persistent and 1,046 (35.5%) were nonpersistent. Compared with nonpersistent patients, persistent patients were older (49.2 vs. 45.5 years; P < 0.001) and more likely to be male (52% vs. 45%; P < 0.001). More persistent patients were diagnosed with dyslipidemia (40% vs. 35%; P = 0.002), had lower antidepressant use (23.4% vs. 27.4%; P < 0.001), and had lower anxiolytic use (30% vs. 37%; P < 0.001) compared with nonpersistent patients. After adjusting for demographic and clinical characteristics, nonpersistent patients had higher total medical costs ($12,457 vs. $8,964; P < 0.001) compared with persistent patients, and ambulatory visits (23.9 vs. 21.4; P = 0.007) were a major contributor. Approximately 40% of the total overall medical costs were attributed to psoriasis and PsA. Although persistent patients incurred higher pharmacy costs ($10,684 vs. $7,849; P < 0.001) due to higher biologic use and the potentially high per-unit cost of biologics, their psoriasis- and/or PsA-related medical costs were significantly lower than those of nonpersistent patients ($3,395 vs. $5,041; P < 0.001). Total overall costs combining medical and pharmacy costs were similar between the cohorts ($22,678 vs. $21,477; P = 0.122). CONCLUSIONS: Moderate to severe psoriasis and/or PsA patients who were persistent on index biologic treatment had higher pharmacy utilization and costs, albeit with lower medical costs and similar total costs, compared with nonpersistent patients. DISCLOSURES: This study was funded by Janssen Scientific Affairs. Lee is a paid employee of Janssen Scientific Affairs. Xie, Wang, Vaidya, and Baser are paid employees of STATinMED Research, which is a paid consultant to Janssen Scientific Affairs. This study was presented as an abstract at the Academy of Managed Care Pharmacy 2017 Annual Meeting, March 27-30, 2017, in Denver, CO.

Effectiveness and Safety of Anticoagulants in Adults with Non-valvular Atrial Fibrillation and Concomitant Coronary/Peripheral Artery Disease.

BACKGROUND: Direct oral anticoagulants (DOAC) are at least non-inferior to warfarin in efficacy and safety among patients with nonvalvular atrial fibrillation. Limited evidence is available regarding outcomes for nonvalvular atrial fibrillation patients with coronary/peripheral artery disease. METHODS: Non-valvular atrial fibrillation patients aged ≥65 years diagnosed with coronary/peripheral artery disease in the US Medicare population, newly initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected from January 1, 2013 to September 30, 2015. Propensity score matching was used to compare DOACs vs warfarin. Cox proportional hazards models were used to estimate the risk of stroke/systemic embolism, major bleeding, and composite of stroke/myocardial infarction/all-cause mortality. RESULTS: There were 15,527 apixaban-warfarin, 6,962 dabigatran-warfarin, and 25,903 rivaroxaban-warfarin-matched pairs, with a mean follow-up of 5-6 months. Compared with warfarin, apixaban was associated with lower rates of stroke/systemic embolism (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.37-0.62), major bleeding (HR 0.66; 95% CI, 0.58-0.75), and stroke/myocardial infarction/all-cause mortality (HR 0.63; 95% CI, 0.58-0.69); dabigatran and rivaroxaban were associated with lower rates of stroke/myocardial infarction/all-cause mortality (HR 0.79; 95% CI, 0.70-0.90 and HR 0.87; 95% CI, 0.81-0.92, respectively). Rivaroxaban was associated with a lower rate of stroke/systemic embolism (HR 0.72; 95% CI, 0.60-0.89) and a higher rate of major bleeding (HR 1.14; 95% CI, 1.05-1.23) vs warfarin. CONCLUSIONS: All DOACs were associated with lower stroke/myocardial infarction/all-cause mortality rates compared with warfarin; differences were observed in rates of stroke/systemic embolism and major bleeding. Findings from this observational analysis provide important insights about oral anticoagulation therapy among non-valvular atrial fibrillation patients with coronary/peripheral artery disease and may help physicians in the decision-making process when treating this high-risk group of patients.

Cytoreductive treatment patterns among US veterans with polycythemia vera.

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased thrombotic and cardiovascular risk, which are key contributors to patient morbidity and mortality. The Veterans Health Administration (VHA) is the largest integrative health network in the United States. Available data concerning patients with PV in this population are limited. METHODS: This retrospective observational study evaluated the characteristics, management, and outcomes of patients with PV in the VHA Medical SAS® Dataset (October 1, 2005, to September 30, 2012). Inclusion criteria were ≥ 2 claims for PV (ie, PV diagnostic code was recorded) ≥30 days apart during the identification period, age ≥ 18 years, and continuous health plan enrollment from ≥12 months before the index date until the end of follow-up. All data were analyzed using descriptive statistics. RESULTS: The analysis included 7718 patients (median age, 64 years; male, 98%; white, 64%). The most common comorbidities before the index date were hypertension (72%), dyslipidemia (54%), and diabetes (24%); 33% had a history of smoking. During the follow-up period (median, 4.8 years), most patients did not receive treatment with cytoreductive therapy, including phlebotomy (53%), or antiplatelet agents, such as aspirin (57%). The thrombotic and cardiovascular event rates per 1000 patient-years were 60.5 and 83.8, respectively. Among patients who received cytoreductive treatment, the thrombotic event rate was 48.9 per 1000 patient-years. The overall mortality rate was 51.2 per 1000 patient-years. CONCLUSION: The notable rates of thrombotic and cardiovascular events observed in this analysis, even among patients receiving cytoreductive treatment, highlight the important unmet clinical needs of patients with PV in the VHA.

Comorbidity and economic burden among moderate-to-severe psoriasis and/or psoriatic arthritis patients in the US Department of Defense population.

AIMS: To examine the comorbidity and economic burden among moderate-to-severe psoriasis (PsO) and/or psoriatic arthritis (PsA) patients in the US Department of Defense (DoD) population. MATERIALS AND METHODS: This retrospective cohort claims analysis was conducted using DoD data from November 2010 to October 2015. Adult patients with ≥2 diagnoses of PsO and/or PsA (cases) were identified, and the first diagnosis date from November 2011 to October 2014 was defined as the index date. Patients were considered moderate-to-severe if they had ≥1 non-topical systemic therapy or phototherapy during the 12 months pre- or 1 month post-index date. Patients without a PsO/PsA diagnosis during the study period (controls) were matched to cases on a 10:1 ratio based on age, sex, region, and index year; the index date was randomly selected. One-to-one propensity score matching (PSM) was conducted to compare study outcomes in the first year post-index date, including healthcare resource utilization (HRU), costs, and comorbidity incidence. RESULTS: A total of 7,249 cases and 72,490 controls were identified. The mean age was 48.1 years. After PSM, comorbidity incidence was higher among cases, namely dyslipidemia (18.3% vs 13.5%, p < .001), hypertension (13.8% vs 8.7%, p < .001), and obesity (8.8% vs 6.1%, p < .001). Case patients had significantly higher HRU and costs, including inpatient ($2,196 vs $1,642; p < .0016), ambulatory ($8,804 vs 4,642; p < .001), emergency room ($432 vs $350; p < .001), pharmacy ($6,878 vs $1,160; p < .001), and total healthcare costs ($18,311 vs $7,795; p < .001). LIMITATIONS: Claims data are collected for payment purposes; therefore, such data may have limitations for clinical research. CONCLUSIONS: During follow-up, DoD patients with moderate-to-severe PsO and/or PsA experienced significantly higher HRU, cost, and comorbidity burden.

Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population.

OBJECTIVE: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients. METHODS: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts. RESULTS: Of the 186,132 eligible patients, 20,803 apixaban-warfarin pairs, 52,476 rivaroxaban-warfarin pairs, and 16,731 dabigatran-warfarin pairs were matched. Apixaban (hazard ratio [HR] = 0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR = 0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.51; 95% CI 0.44, 0.58) and dabigatran (HR = 0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR = 1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs. CONCLUSIONS: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.

Overall Effectiveness of Rivaroxaban in Patients with Pulmonary Embolism.

PURPOSE: Due to limited evidence on the impact of rivaroxaban in clinical practice, we compared the effectiveness of rivaroxaban versus standard of care (SOC) among patients in the Veterans Health Administration. METHODS: Adult patients with continuous enrollment in a health plan with medical and pharmacy benefits for ≥12 months before and ≥3 months after an inpatient diagnosis of pulmonary embolism (PE) between October 1, 2011, and June 30, 2015, and a prescription claim for an anticoagulant during the index hospitalization, were included. SOC drugs were low-molecular-weight heparin, unfractionated heparin, and warfarin. Propensity score matching was used in comparing PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), hospital-acquired complications (HACs), health care resource utilization, and costs among patients receiving SOC versus rivaroxaban. We defined net clinical benefit as 1 minus the combined rate of PE-related outcomes and HACs. FINDINGS: Among 6746 patients with PE, 208 received rivaroxaban, 4641 received SOC and 1897 received other anticoagulants. Most (95%) were male; 22% were black. After 1:3 propensity score matching, there were 203 rivaroxaban and 609 SOC patients. During the 90-day follow-up, rivaroxaban users had similar rates of PE-related outcomes, but fewer had experienced at least 1 HAC (10.3% vs 15.9%; P = 0.0506), resulting in better net clinical benefit (82.8% vs 71.1%; P = 0.001). Rivaroxaban users had fewer outpatient visits per patient (17.0 vs 19.9; P = 0.0005), a similar rehospitalization rate (0.2 vs 0.3; P = 0.084), lesser inpatient costs (US $3501 vs $6189; P < 0.0001), lesser inpatient costs and lesser total costs ($10,545 vs $14,192; P = 0.0002). When the sample was limited to patients with low-risk PE, we found similar patterns. IMPLICATIONS: Patients with PE prescribed rivaroxaban had similar PE-related outcomes, but fewer HACs and lesser total costs, than did patients on SOC.

Cancer chemotherapy treatment patterns and febrile neutropenia in the US Veterans Health Administration.

BACKGROUND: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States and a major cancer care provider. OBJECTIVE: To use VHA database to conduct a population-based study of patterns of myelosuppressive chemotherapy use and to assess the incidence and management of febrile neutropenia (FN) among VHA patients with lung, colorectal, or prostate cancer or non-Hodgkin lymphoma (NHL). METHODS: Data were extracted for the initial myelosuppressive chemotherapy course for 27,899 patients who began treatment in the period 2006 to 2011. FN-related costs were defined as claims containing FN diagnosis. RESULTS: Most patients were men (98.0%); most were 65 years or older (55.8%). Patients received a mean 3.4 to 3.9 chemotherapy cycles/course (median cycle duration 34-43 days). The incidence of FN among patients with lung, colorectal, or prostate cancer or NHL was 10.2%, 4.6%, 5.4%, and 17.3%, respectively. Primary or secondary prophylactic antibiotics/colony-stimulating factors were received by 21% and 12% of patients, respectively. Antibiotics were more commonly given as primary or secondary prophylaxis for patients with lung, colorectal, and prostate cancer; colony-stimulating factors were more common for patients with NHL. Among patients with FN, those with lung cancer had the highest inpatient mortality (10%); patients with NHL had the highest costs ($24,571) and the longest hospital length of stay (15.4 days). CONCLUSIONS: VHA cancer care was generally consistent with National Comprehensive Cancer Network recommendations; however, compared with the general population, chemotherapy cycles were longer, combination chemotherapy was used less, and treatment to prevent FN was used less, differences that may be attributed to the unique VHA patient population. The impact of these practices warrants further investigation.

Health care cost associated with prostate cancer, androgen deprivation therapy and bone complications.

PURPOSE: We ascertained the health care costs of androgen deprivation therapy and related skeletal events. MATERIALS AND METHODS: Using data from the MarketScan Medicare Supplemental and Coordination of Benefits Database, we identified cases with International Classification of Disease, 9th Revision codes indicating a diagnosis of prostate cancer who initiated androgen deprivation therapy between 1999 and 2002. The control group consisted of patients with prostate cancer with no androgen deprivation therapy use, matched by age, geographic region, insurance plan and index year. All had followup data for at least 36 months. The occurrence and cost of osteoporosis and any bone fracture were assessed using a propensity score matched sample. RESULTS: Of the 8,577 eligible men with prostate cancer, 3,055 initiated androgen deprivation therapy and 5,522 did not. At the time of androgen deprivation therapy initiation those on androgen deprivation therapy had more severe comorbidity (3.1 vs 2.6, p <0.001) and proportionally more bone metastases (2.8% vs less than 0.6%, p <0.001) but no difference in fracture rate. After 3 years of followup the androgen deprivation therapy group experienced significantly more fractures (18.7% vs 14.6%, p <0.001). The mean unadjusted total cost of health care during the 36-month period was $48,350 per person for cases and $26,097 for controls. CONCLUSIONS: Among men with prostate cancer, those on androgen deprivation therapy cost the health care system almost twice as much as those not on androgen deprivation therapy. After controlling for differences in health status, the majority of the excess cost is attributable to androgen deprivation therapy and then to a lesser extent, the fractures. These results suggest that the bone complications of osteoporosis and fractures in men on androgen deprivation therapy have important economic consequences.